The regional cerebral metabolic rate for glucose (rCMRglc) was examined in awake Fischer-344 rats in relation to age, pharmacological stimulation and behavior. The lumped constant used to calculate rCMRglc was shown to decline with age in Fischer-344 rats. Arecoline, a cholinergic agonist, stimulated rCMRglc in a number of brain regions, including those with muscarinic receptors. Cerebral metabolic responses were not reduced in senescent animals, indicating maintenance of postsynaptic cholinergic function. Metabolic responses to nicotine, another cholinergic agonist, were consistent with the distribution of nicotinic receptors within the rat brain. Dopaminergic function in the rat brain was examined by measuring rCMRglc in response to haloperidol (a dopaminergic antagonist), bromocriptine (an agonist) and sulpiride (a specific antagonist). The response to haloperidol was reduced in senescent as compared to younger rats, despite higher brain concentrations of haloperidol in the older animals, suggesting a reduced central dopaminergic function, and an imbalance between the cholinergic and dopaminergic systems in the brain of the senescent rat. Metabolic responses to haloperidol depended on time after treatment, and demonstrated tolerance after long-term administration. Regional cerebral blood flow (rCBF) was age invariant in awake Beagles between 1 and 12 years, and declined only in extreme senescence in relation to systemic disease, suggesting that cerebral functional activity is maintained during the life span of the healthy Beagle.